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Background: Optimal timing of the atrioventricular delay in cardiac resynchronization therapy (CRT) can improve synchrony in patients suffering from heart failure. The purpose of this study was to evaluate the impact of SyncAV™ on electrical synchrony as measured by vectorcardiography (VCG) derived QRS metrics during bi-ventricular (BiV) pacing. Methods: Patients implanted with a cardiac resynchronization therapy (CRT) device and quadripolar left ventricular (LV) lead underwent 12‑lead ECG recordings. VCG metrics, including QRS duration (QRSd) and area, were derived from the ECG by a blinded observer during: intrinsic conduction, BiV with nominal atrioventricular delays (BiV Nominal), and BiV with SyncAV programmed to the optimal offset achieving maximal synchronization (BiV + SyncAV Opt). Results: One hundred patients (71% male, 40% ischemic, 65% LBBB, 32 ± 9% ejection fraction) completed VCG assessment. QRSd during intrinsic conduction (166 ± 25 ms) was narrowed successively by BiV Nominal (137 ± 23 ms, p

Background and Objectives: Conduction disturbances such as left bundle branch block (LBBB) and complete atrio-ventricular block (cAVB) are relatively frequent complications following trans-catheter aortic valve implantation (TAVI). We investigated the dynamics of these conduction blocks to further understand luxating factors and predictors for their persistency. Materials and Methods: We prospectively included 157 consecutive patients who underwent a TAVI procedure. Electrocardiograms (ECGs) were obtained at specific time points during the TAVI procedure and at follow-up until at least six months post-procedure. Results: Of the 106 patients with a narrow QRS complex (nQRS) before TAVI, ~70% developed LBBB, 28 (26.4%) being classified as super-transient (ST-LBBB), 20 (18.9%) as transient (T-LBBB) and 24 (22.6%) as persistent (P-LBBB). Risk of LBBB was higher for self-expandable (SE) than for balloon-expandable (BE) prostheses and increased with larger implant depth. During the TAVI procedure conduction disturbances showed a dynamic behavior, as illustrated by alternating kinds of blocks in 18 cases. Most LBBBs developed during balloon aortic valvuloplasty (BAV) and at positioning and deployment of the TAVI prosthesis. The incidence of LBBB was not significantly different between patients who did and did not undergo BAV prior to TAVI implantation (65.3% and 74.2%, respectively (p = 0.494)). Progression to cAVB was most frequent for patients with preexisting conduction abnormalities (5/34) patients) and in patients showing ST-LBBB (6/28). Conclusions: During the TAVI procedure, conduction disturbances showed a dynamic behavior with alternating types of block in 18 cases. After a dynamic period of often alternating types of block, most BBBs are reversible while one third persist. Patients with ST-LBBB are most prone to progressing into cAVB. The observation that the incidence of developing LBBB after TAVI is similar with and without BAV suggests that a subgroup of patients has a substrate to develop LBBB regardless of the procedure.

BACKGROUND Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated.OBJECTIVES The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients.METHODS Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax).RESULTS As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 +/- 22 mu Vs) and SDAT (to 26 +/- 7 ms) than BiV (to 93 +/- 26 mVs and 31 +/- 7 ms; both p CONCLUSIONS LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT. (C) 2020 by the American College of Cardiology Foundation.

Aims Left ventricular (LV) fusion pacing appears to be at least as beneficial as biventricular pacing in cardiac resynchronization therapy (CRT). Optimal LV fusion pacing critically requires adjusting the atrioventricular (AV)-delay to the delay between atrial pacing and intrinsic right ventricular (RV) activation (Ap-RV). We explored the use of electrogram (EGM)-based vectorloop (EGMV) derived from EGMs of implanted pacing leads to achieve optimal LV fusion pacing and to compare it with conventional approaches.Methods and results During CRT-device implantation, 28 patients were prospectively studied. During atrial-LV pacing (Ap-LVp) at various AV-delays, LV dP/dt(max), 12-lead electrocardiogram (ECG), and unipolar EGMs were recorded. Electrocardiogram and electrogram were used to reconstruct a vectorcardiogram (VCG) and EGMV, respectively, from which the maximum QRS amplitude (QRS(ampl)), was extracted. Ap-RV was determined: (i) conventionally as the longest AV-delay at which QRS morphology was visually unaltered during RV pacing at increasing AV-delays( Ap-RVvis; reference-method); (ii) 70% of delay between atrial pacing and RV sensing (Ap-RVaCRT); and (iii) the delay between atrial pacing and onset of QRS (Ap-QRS(onset)). In both the EGMV and VCG, the longest AV-delay showing an unaltered QRS(ampl) as compared with Ap-LVp with a short AV-delay, corresponded to Ap-RVvis. In contrast, Ap-QRS(onset) and Ap-RVaCRT were larger. The Ap-LVp induced increase in LV dP/dt(max) was larger at Ap-RVvis, Ap-RVEGMV, and Ap-RVVCG than at Ap-QRS(onset) (all P Conclusion In this acute study, it is shown that the EGMV QRSampl can be used to determine optimal and individual CRT-device settings for LV fusion pacing, possibly improving long-term CRT response.

Contains fulltext : 200177.pdf (Publisher’s version ) (Open Access) BACKGROUND: The recently developed quadripolar left ventricular (LV) leads have been developed to increase the benefit of cardiac resynchronization therapy (CRT). These leads offer the option to stimulate the LV on multiple sites (multipoint pacing, MPP). Invasive haemodynamic measurements have shown that MPP increases haemodynamic response. PURPOSE: To investigate whether the beneficial effect of MPP can be explained by better electrical resynchronization. METHODS: Different LV lead locations were tested during biventricular (BiV) pacing and MPP in 29 CRT candidates. The 12-lead electrocardiogram (ECG) and the invasive LV pressure curves were measured simultaneously. The Kors matrix was used to convert the ECG into a vectorcardiogram (VCG). The acute haemodynamic benefit of MPP was compared with the reduction in QRS duration and VCG-derived QRS area. RESULTS: Out of the 29 patients, three patients were excluded due to missing LV pressures or ECG measurements. In the remaining 26 patients MPP resulted in a significant haemodynamic improvement compared to BiV pacing without a significant change in QRS duration and QRS area. In only 5 out of the 26 patients the QRS area decreased during MPP compared to BiV pacing. In 17 patients MPP did not change QRS duration and significantly increased QRS area but moved the direction of the maximal QRS vector (azimuth) more opposite from baseline compared to BiV pacing. In 4 patients the QRS area was small during baseline, indicating limited electrical dyssynchrony. CONCLUSION: The acute haemodynamic benefit of MPP over BiV pacing is achieved by either electrical resynchronization (reduction in QRS area) or by a rotation of the maximal QRS vector, indicating a more LV dominated activation sequence. The latter property was found in two-thirds of the cohort studied.

Introduction Proper optimization of atrioventricular (AV) and interventricular (VV) intervals can improve the response to cardiac resynchronization therapy (CRT). It has been demonstrated that the area of the QRS complex (QRSarea) extracted from the vectorcardiogram can be used as a predictor of optimal CRT-device settings. We explored the possibility of extracting vectors from the electrograms (EGMs) obtained from pacing electrodes and of using these EGM-based vectors (EGMVs) to individually optimize acute haemodynamic CRT response. Methods and Results Biventricular pacing was performed in 13 dogs with left bundle branch block (LBBB) of which 5 also had myocardial infarction (MI), using 100 randomized AV- and VV-settings. Settings providing an acute increase in LV dP/dtmax ≥ 90% of the highest achieved value were defined as optimal. The prediction capability of QRSarea derived from the EGMV (EGMV-QRSarea) was compared with that of QRS duration. EGMV-QRSarea strongly correlated to the change in LV dP/dtmax (R = -0.73±0.19 [LBBB] and -0.66±0.14 [LBBB+MI]), while QRS duration was more poorly related to LV dP/dtmax changes (R = -0.33±0.25 [LBBB] and -0.47±0.39 [LBBB+MI]). This resulted in a better prediction of optimal CRT-device settings by EGMV-QRSarea than by QRS duration (LBBB: AUC = 0.89[0.86–0.93] vs. 0.76[0.69–0.83], P

Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response.The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar.Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline.Integration of EAM and DE-CMR was achieved using 8.9 ± 2.8 anatomic landmarks and with accuracy of 4.7 ± 1.1 mm (mean ± SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 ± 3.45 mV vs 8.18 ± 4.02 mV [median ± interquartile range), P.001) but correlated weakly with DE-CMR scar extent (R -0.161, P.001) and varied widely among individual patients.Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT.

Investigations of two chicken processing plants in The Netherlands have shown that large contamination with Campylobacter jejuni can exist on birds, equipment, hands of processing-line workers and in air samples from the processing facility. This contamination appeared only to be of intestinal origin. Intestinal contents of birds to be processed contained up to 107 C. jejuni per gram. Contamination of birds was reduced during scalding at 58°C, but this reduction was not always observed at 51.8°C. The number of C. jejuni on carcasses increased during defeathering and evisceration. Large numbers of C. jejuni were washed off the carcasses when a spinchiller was used. When air-cooling was employed, C. jejuni in some instances died off, probably due to drying. End-products from these chicken processing plants contained C. jejuni in 50% of carcasses and 75% of livers.

A survey was done on the occurrence of Campylobacter jejuni in slaughtered cattle and raw milk from dairy farms in The Netherlands, In the first part of the survey, in which direct plating techniques were used, no C. jejuni was detected in any of 200 samples of caecal contents of cattle or in 200 samples of raw milk. A second series of investigations was done using a new enrichment procedure. This time C. jejuni was isolated from 11 of 200 caecal contents, but from none of 200 samples of milk. Further experiments showed that Campylobacter can survive in milk at 4°C for weeks, whether the milk was shaken with air (as occurs during the milking process) or not. Our investigations indicate that C. jejuni was not excreted with the milk. It can be concluded that cattle in The Netherlands do not play an important role in the epidemiology of C. jejuni .

Aims Left bundle branch block (LBBB) is induced in approximately one-third of all transcatheter aortic valve implantation (TAVI) procedures. We investigated electrophysiological remodelling in patients with TAVI-induced LBBB. Methods and results This retrospective study comprises 107 patients with initially narrow QRS complex of whom 40 did not and 67 did develop persistent LBBB after TAVI. 12-lead electrocardiograms (ECGs) taken before TAVI, within 24 hours (‘acute’), and 1–12 months after TAVI (‘chronic’) were used to reconstruct vectorcardiograms. From these vectorcardiograms, QRS and T-wave area were calculated as comprehensive indices of depolarization and repolarization abnormalities, respectively. TAVI-induced LBBB resulted in significant acute depolarization and repolarization changes while further repolarization changes were observed with longer lasting LBBB. The amount of long-term repolarization changes (remodelling) was highly variable between patients. The change in T-wave area between acute and chronic LBBB ranged from +57% to − 77%. After dividing the LBBB cohort into tertiles based on the change in T-wave area, only baseline QRS area was larger in the tertile with no significant change in T-wave area. During longer lasting LBBB, the spatial vector gradient (SVG) changed orientation towards the direction of the QRS-vector, indicating that later-activated regions developed shorter action potential duration. Conclusion This study in patients with TAVI-induced LBBB shows that repolarization changes develop within months after onset of LBBB, and that these changes are highly variable between individual patients.

Cardiac resynchronization therapy (CRT) is a well-known treatment modality for patients with a reduced left ventricular ejection fraction accompanied by a ventricular conduction delay. However, a large proportion of patients does not benefit from this therapy. Better patient selection may importantly reduce the number of non-responders. Here, we review the strengths and weaknesses of the electrocardiogram (ECG) markers currently being used in guidelines for patient selection, e.g., QRS duration and morphology. We shed light on the current knowledge on the underlying electrical substrate and the mechanism of action of CRT. Finally, we discuss potentially better ECG-based biomarkers for CRT candidate selection, of which the vectorcardiogram may have high potential.

Background: The combination of left bundle branch block (LBBB) morphology and QRS duration is currently used to select patients for cardiac resynchronization therapy (CRT). These parameters, however, have limitations. This study evaluates the value of QRS area compared with that of QRS duration and morphology in the association with clinical and echocardiographic outcomes in a large cohort of CRT patients. Methods: A retrospective multicentre study was conducted in 1492 CRT patients. LBBB morphology, QRS duration, and QRS area in the baseline 12-lead ECG were evaluated for their association with the occurrence of the combined primary end point of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation. Secondary end points were heart failure hospitalization within the first year after implantation and echocardiographic reduction in left ventricular end-systolic volume. Results: During a mean follow-up period of 3.4 years, 32% of patients reached the primary end point. The association of QRS area with all outcomes was stronger than that of LBBB morphology and QRS duration separately and at least as strong as their combination. QRS area identified patients who did not experience the primary end point better than QRS morphology and QRS duration (area under the curve, 0.61 versus 0.55 and 0.51, respectively; P P Conclusions: QRS area has a strong association to clinical and echocardiographic response to CRT, at least as strong as current patient selection parameters. QRS area may be particularly useful to predict CRT response in patients without a wide LBBB.

Contains fulltext : 200363.pdf (Publisher’s version ) (Open Access) PURPOSE: To investigate the relationship between vectorcardiography (VCG) and myocardial scar on cardiac magnetic resonance (CMR) imaging, and whether combining these metrics may improve cardiac resynchronization therapy (CRT) response prediction. METHODS: Thirty-three CRT patients were included. QRSarea, Tarea and QRSTarea were derived from the ECG-synthesized VCG. CMR parameters reflecting focal scar core (Scar2SD, Gray2SD) and diffuse fibrosis (pre-T1, extracellular volume [ECV]) were assessed. CRT response was defined as >/=15% reduction in left ventricular end-systolic volume after six months' follow-up. RESULTS: VCG QRSarea, Tarea and QRSTarea inversely correlated with focal scar (R=-0.44--0.58 for Scar2SD, p

Background The use of vectorcardiography (VCG) has regained interest, however, original Frank-VCG equipment is rare. This study compares the measured VCGs with those synthesized from the 12-lead electrocardiogram (ECG) in patients with heart failure and conduction abnormalities, who are candidate for cardiac resynchronization therapy (CRT). Methods In 92 CRT candidates, Frank-VCG and 12-lead ECG were recorded before CRT implantation. The ECG was converted to a VCG using the Kors method (Kors-VCG) and the two methods were compared using correlation and Bland–Altman analyses. Results Variables calculated from the Frank- and Kors-VCG showed correlation coefficients between 0.77 and 0.90. There was a significant but small underestimation by the Kors-VCG method, relative bias ranging from − 1.9% ± 4.6% (QRS-T angle) to − 9.4% ± 20.8% (T area). Conclusion The present study shows that it is justified to use Kors-VCG calculations for VCG analysis, which enables retrospective VCG analysis of previously recorded ECGs in studies related to CRT.

To investigate the relationship between vectorcardiography (VCG) and myocardial scar on cardiac magnetic resonance (CMR) imaging, and whether combining these metrics may improve cardiac resynchronization therapy (CRT) response prediction.Thirty-three CRT patients were included. QRSVCG QRSQRS

T-Wave Predicts CRT Response in LBBB Patients Introduction Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30–50% of patients do not show a clear response to CRT. We investigated whether T-wave analysis of the ECG can improve patient selection. Methods and Results The study population comprised 244 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-month CRT was defined as a ≥5% increase in LV ejection fraction (LVEF). Vectorcardiograms (VCGs) were constructed from the measured 12-lead ECGs using an adapted Kors algorithm on digitized ECGs. Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio [OR] per 10 μVs increase 1.172 [P < 0.001]) even better than QRS-wave area (OR = 1.116 [P = 0.001]). T-wave area had especially predictive value in the LBBB patient group (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment of multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and β-blockers. In LBBB patients, the increase in LVEF was 6.1 ± 9.7% and 11.3 ± 9.1% in patients with T-wave area below and above the median value, respectively (P < 0.01). Conclusion In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important independent predictor of LVEF increase following CRT.

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We present new schemes to improve the convergence of an important global optimization problem and to determine reaction pathways (RPs) between identified minima. Those methods have been implemented into the CAST program (Conformational Analysis and Search Tool). The first part of this chapter shows how to improve convergence of the Monte Carlo with minimization (MCM, also known as Basin Hopping) method when applied to optimize water clusters or aqueous solvation shells using a simple model. Since the random movement on the potential energy surface (PES) is an integral part of MCM, we propose to employ a hydrogen bonding-based algorithm for its improvement. We show comparisons of the results obtained for random dihedral and for the proposed random, rigid-body water molecule movement, giving evidence that a specific adaption of the distortion process greatly improves the convergence of the method. The second part is about the determination of RPs in clusters between conformational arrangements and for reactions. Besides standard approaches like the nudged elastic band method, we want to focus on a new algorithm developed especially for global reaction path search called Pathopt. We started with argon clusters, a typical benchmark system, which possess a flat PES, then stepwise increase the magnitude and directionality of interactions. Therefore, we calculated pathways for a water cluster and characterize them by frequency calculations. Within our calculations, we were able to show that beneath local pathways also additional pathways can be found which possess additional features.

Aims There is increasing evidence that left bundle branch block (LBBB) morphology on the electrocardiogram is a positive predictor for response to cardiac resynchronization therapy (CRT). We previously demonstrated that the vectorcardiography (VCG)-derived T-wave area predicts echocardiographic CRT response in LBBB patients. In the present study, we investigate whether the T-wave area also predicts long-term clinical outcome to CRT. Methods and results This is a retrospective study consisting of 335 CRT recipients. Primary endpoint were the composite of heart failure (HF) hospitalization, heart transplantation, left ventricular assist device implantation or death during a 3-year follow-up period. HF hospitalization and death alone were secondary endpoints. The patient subgroup with a large T-wave area and LBBB 36% reached the primary endpoint, which was considerably less (P

To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies.Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation.Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia).The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.

Der Arbeitsausschuss NA 014-00-21 AA ”Dentalimplantate“ im DIN (Deutsches Institut fur Normung) ist in Deutschland dafur zustandig, den wachsenden Markt der Insertion von Dentalimplantaten zu regeln. Unter der Federfuhrung des Vorsitzenden Prof. Klaus Dermann und seines Stellvertreters Dr. Helmut B. Engels bearbeitet der Ausschuss die Normung von enossalen Dentalimplantaten, Membranen sowie von Abutments. Die Bundeszahnarztekammer nimmt aufgrund der Bestellung von Experten an zahlreichen Normungsvorhaben im dentalen Bereich rege Anteilnahme. Ziel der Normung ist es, sowohl fur Zahnmediziner als auch fur Patienten Produktsicherheit herzustellen. Denn ohne die Prozeduren der DIN-, CEN- oder ISO-Normen kommt kein Implantat oder Instrumentarium auf den Markt. Das MPG (Medizinproduktegesetz) uberwacht die geforderten Kriterien angefangen bei der Oberflachenbeschaffenheit bis hin zur Ermudungsbruchtestung.

Multi point pacing (MPP) with a quadripolar left ventricular (LV) lead may increase response to cardiac resynchronization therapy (CRT), although factors associated with response to MPP are unknown. Heart failure patients with a left bundle branch block were analyzed during CRT implantation with a

Objective: To clarify the practice of end-of-life decision making in severely ill newborns.Design: Retrospective descriptive study with face-to-face interviews.Setting: The 10 neonatal intensive care units in the Netherlands from October 2005 to September 2006.Patients: All 367 newborn infants who died in the first 2 months of life in Dutch neonatal intensive care units. Adequate documentation was available in 359 deaths.Outcome Measures: Presence of end-of-life decisions, classification of deaths in 3 groups, and physicians' considerations leading to end-of-life decisions.Results: An end-of-life decision preceded death in 95% of cases, and in 5% treatment was continued until death. Of all of the deaths, 58% were classified as having no chance of survival and 42% were stabilized newborns with poor prognoses. Withdrawal of life-sustaining therapy was the main mode of death in both groups. One case of deliberate ending of life was found. In 92% of newborns with poor prognoses, end-of-life decisions were based on patients' future quality of life and mainly concerned future suffering. Considerations regarding the infant's present state were made in 44% of infants.Conclusions: Virtually all deaths in Dutch neonatal intensive care units are preceded by the decision to withdraw life-sustaining treatment and many decisions are based on future quality of life. The decision to deliberately end the life of a newborn may occur less frequently than was previously assumed.

Partial remission of a centroblastic non-Hodgkin's lymphoma, clinical stage IV A, in a 79-year-old man was achieved by six courses of chemotherapy with epirubicin, cyclophosphamide and vincristine. The only residual finding was a palpable small cervical lymphoma. After a treatment pause of about 6 weeks increasing hypersalivation set in which ultimately made food intake impossible and led to a breakdown in the patient's general state. Findings in the region of the head, neck, throat and the base of the skull were unremarkable, but cerebrospinal fluid contained 1300/3 cells, almost all of them lymphoblasts. After five intrathecal injections of at first 15 mg methotrexate and 4 mg dexamethasone each, followed by five more with 40 mg cytarabine added to them, the CSF cell count became normal. At the same time salivation clearly decreased and food intake became once again possible. The patient died 5 months later from hypercalcaemia due to osseous infiltrations. Until his death there was no recurrence of the hypersalivation as the cardinal sign of meningeal carcinomatosis.

The intestinal parasites Cryptosporidium and Giardia cause gastro-enteritis in humans and can be transmitted via contaminated water. Oysters are filter feeders that have been demonstrated to accumulate pathogens such as Salmonella, Vibrio, norovirus and Cryptosporidium from contaminated water and cause foodborne infections. Oysters are economically important shellfish that are generally consumed raw. Commercial and non-commercial oysters (Crassostrea gigas) and oyster culture water from the Oosterschelde, The Netherlands, were examined for the presence of Cryptosporidium oocysts and Giardia cysts. Nine of 133 (6.7%) oysters from two non-commercial harvesting sites contained Cryptosporidium, Giardia or both. Six of 46 (13.0%) commercial oysters harboured Cryptosporidium or Giardia in their intestines. Data on the viability of (oo)cysts recovered from Oosterschelde oysters were not obtained, however viable (oo)cysts were detected in surface waters that enter the Oosterschelde oyster harvesting areas. The detection of Cryptosporidium and Giardia in oysters destined for human consumption has implications for public health only when human pathogenic (oo)cysts that have preserved infectivity during their stay in a marine environment are present. Our data suggest that consumption of raw oysters from the Oosterschelde may occasionally lead to cases of gastro-intestinal illness.

Delayed left ventricular (LV) lateral wall (LVLW) activation is considered the electrical substrate underlying LV dysfunction amenable to cardiac resynchronization therapy (CRT).The purpose of this study was to assess LVLW activation in CRT candidates using coronary venous electroanatomic mapping (EAM) and to investigate whether the QRS area (QRSAREA) on the vectorcardiogram (VCG) can identify delayed LVLW activation.Fifty-one consecutive CRT candidates (29 left bundle branch block [LBBB], 15 intraventricular conduction delay [IVCD], 7 right bundle branch block [RBBB]) underwent intraprocedural coronary venous EAM using EnSite NavX. VCGs were constructed from preprocedural digital 12-lead ECGs using the Kors method. QRSAREA was assessed and compared to QRS duration and 5 different LBBB definitions.Delayed LVLW activation (activation time75% of QRS duration) occurred in 38 of 51 patients (29/29 LBBB, 8/15 IVCD, 1/7 RBBB). QRSAREA was larger in patients with than in patients without delayed LVLW activation (108 ± 42 µVs vs 51 ± 27 µVs, P.001), and identified delayed LVLW activation better than QRS duration (area under the curve 0.89 [95% confidence interval 0.79-0.99] vs 0.49 [95% confidence interval 0.33-0.65]). QRSAREA69 µVs diagnosed delayed LVLW activation with a higher sum of sensitivity (87%) and specificity (92%) than any of the LBBB definitions. Of the different LBBB definitions, the European Society of Cardiology textbook definition performed best with sensitivity of 76% and specificity of 100%.Coronary venous EAM can be used during CRT implantation to determine the presence of delayed LVLW activation. QRSAREA is a noninvasive alternative for intracardiac measurements of electrical activation, which identifies delayed LVLW activation better than QRS duration and LBBB morphology.

In the past few years many waterborne outbreaks related to Cryptosporidium have been described. Current methods for detection of Cryptosporidium in water for the most part rely on viability assays which are not informative concerning the infectivity of oocysts. However, for estimation of the risk of infection with Cryptosporidium this information is required. For environmental samples the oocyst counts are often low, and the oocysts have been exposed to unfavorable conditions. Therefore, determination of the infectivity of environmental oocysts requires an assay with a high level of sensitivity. We evaluated the applicability of in vitro cell culture immunofluorescence assays with HCT-8 and Caco-2 cells for determination of oocyst infectivity in naturally contaminated water samples. Cell culture assays were compared with other viability and infectivity assays. Experiments with Cryptosporidium oocysts from different sources revealed that there was considerable variability in infectivity, which was illustrated by variable 50% infective doses, which ranged from 40 to 614 oocysts, and the results indicated that not only relatively large numbers of fresh oocysts but also aged oocysts produced infection in cell cultures. Fifteen Dutch surface water samples were tested, and the cell culture immunofluorescence assays were not capable of determining the infectivity for the low numbers of naturally occurring Cryptosporidium oocysts present in the samples. A comparison with other viability assays, such as the vital dye exclusion assay, demonstrated that surrogate methods overestimate the number of infectious oocysts and therefore the risk of infection with Cryptosporidium . For accurate risk assessment, further improvement of the method for detection of Cryptosporidium in water is needed.

The occurrence of Cryptosporidium and Giardia in indoor swimming pools in the Netherlands was studied at five locations. The backwash water from seven pool filters was analysed for the presence of Cryptosporidium oocysts and Giardia cysts for a period of 1 year. Of the 153 samples of filter backwash water analysed, 18 (11.8%) were found positive for either Cryptosporidium (4.6%), Giardia (5.9%) or both (1.3%). Oocysts and cysts were also detected in the water of one toddler pool and one learner pool. Although most of the (oo)cysts in the filter backwash water were dead, viable and potentially infectious oocysts were detected in the learner pool. On the basis of numbers of potentially infectious (oo)cysts detected in the learner pool, and assuming one visit to an infected pool per year, risk assessment indicated an estimated risk of infection with Cryptosporidium that exceeded the generally accepted risk of one infection per 10,000 persons per year. Guidelines for pool operators on how to manage faecal accidents and public information on the importance of hygiene in swimming pool complexes are recommended tools in controlling the risk of infection.

The chemical forms of low concentrations of metals (Zn, Pb, Cu, Cd, Co and Mn) and main components (Fe and Ca) were determined under the original reducing conditions of a sulfide-rich sediment from the Gent-Terneuzen Canal (Belgium). Therefore, dissolution experiments as a function of pH were made in a salt solution mimicking the canal water. The centrifugates remaining after the dissolution vs. pH experiments were subsequently further extracted with 0.1 M EDTA/0.5 M NaAc (pH 4.65) to determine eventually readsorbed and/or reprecipitated metal ions. The experimental dissolution vs. pH edge of calcium, iron, manganese and cobalt had a lower slope than theoretically expected on the basis of the solubility of, respectively, calcium carbonate, iron sulfide/iron carbonate, manganese sulfide/manganese carbonate and cobalt sulfide and was explained by the combination of (a) the solubilities of the various minerals and (b) metal readsorption onto clay minerals and organic matter. Higher metal recoveries were measured in the 0.1 M EDTA/0.5 M NaAc mixture and proved that in addition coprecipitate formation with iron sulfide/iron carbonate minerals may occur. The solubility of zinc, lead, cadmium and copper was very low in the mimicking salt solution even at very low pH values (up to pH 1) in agreement with the theoretical solubility of their discrete metal sulfides. However, by using an additional 0.1 M EDTA/0.5 M NaAc extraction on the centrifugates remaining after the dissolution vs. pH experiments, it was qualitatively shown that zinc and lead were partly associated with iron sulfide/iron carbonate phases in the real sediment (in addition to their presence in discrete metal sulfides). Cadmium was present solely in discrete cadmium sulfide phases. It was not possible to verify whether copper was present in discrete copper sulfide phases and/or in mixed coprecipitates with iron sulfide/iron carbonate minerals.

Purpose: Chronic heart failure (HF) patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), derive benefit from cardiac resynchronization therapy (CRT). However, approximately 30% of patients do not improve clinically after CRT. We investigated whether T-wave analysis can improve patient selection. Methods: The study population comprised 335 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-months CRT was defined as a ≥ 5% increase in LV ejection fraction (LVEF). Patients were assessed for HF hospitalization and death separately, as well as both combined with heart transplantation and LVAD implantation (HTLD) at 3 years follow-up. T-wave area was determined in vectorcardiograms (VCGs), constructed from digital 12-lead ECGs using an adapted Kors method. Results: Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio (OR) per 10 μVs increase 1.172 (p < 0.001)), even better than QRS-wave area (OR = 1.116 (p = 0.001)). T-wave area had especially predictive value in LBBB patients (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment for multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and beta-blockers. The table depicts that patients with large T-wave area showed a larger increase in LVEF and a lower occurrence of the end-points HF hospitalization, death and HTLD, as compared to those with a small T-wave area, the difference being significant for LBBB patients. Conclusions: In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important additional predictor of both volumetric and long-term clinical response following CRT.

Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30-50% of patients do not show a clear response to CRT. We investigated whether T-wave analysis of the ECG can improve patient selection.The study population comprised 244 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-month CRT was defined as a ≥5% increase in LV ejection fraction (LVEF). Vectorcardiograms (VCGs) were constructed from the measured 12-lead ECGs using an adapted Kors algorithm on digitized ECGs. Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio [OR] per 10 μVs increase 1.172 [P0.001]) even better than QRS-wave area (OR = 1.116 [P = 0.001]). T-wave area had especially predictive value in the LBBB patient group (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment of multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and β-blockers. In LBBB patients, the increase in LVEF was 6.1 ± 9.7% and 11.3 ± 9.1% in patients with T-wave area below and above the median value, respectively (P0.01).In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important independent predictor of LVEF increase following CRT.

Objective: To use the System of Objectified Judgement Analysis (SOJA) method for the rational selection of Helicobacter pylori eradication therapies for formulary inclusion. Design: Drug selection for the eradication therapy of H. pylori is made by means of the SOJA method. In this formulary decision-making model, selection criteria for a given class of drugs are prospectively defined and weighted by a panel of experts. The following criteria (relative weight) were used: variability of pharmacokinetics; drug interactions; resistance to antibacterials; efficacy; general adverse effects; complexity of the regimen; acquisition cost and clinical documentation. Only published studies with at least 30 evaluable patients were considered, at least 3 studies had to be available per treatment regimen and efficacy had to be assessed on an intent-to-treat basis. Main outcome measures and results: The regimens containing clarithromycin and an imidazole antibacterial in combination with omeprazole or ranitidine bismutrex showed the highest scores for eradication of H. pylori. The combinations amoxicillin/clarithromycin and omeprazole or lansoprazole showed slightly lower eradication rates and were more costly. The eradication rates obtained with 2-drug regimens were low, resulting in a low overall SOJA score. No quadruple regimens could be included, as none of the regimens fulfilled the inclusion criteria. This was also true for the classical triple therapy with bismuth/metronidazole/tetracycline. Conclusion: The present score is specific for the Netherlands, as Dutch acquisition costs and data on resistance were used. In other countries, with different degrees of imidazole and clarithromycin resistance, other regimens may be more appropriate. The SOJA score will be regularly updated through the internet to include relevant new studies or new successful eradication regimens. The interactive program offers groups of physicians the opportunity to discuss the optimal H. pylori eradication regimen, based on their weighting of the criteria.

Despite three decades of continuous research on gentrification, there are a number of areas where understanding of this process still remains quite rudimentary, especially with respect to the actual process of gentrification itself. The author seeks to focus attention upon this issue by examining how historic change to property ownership and tenure structure of housing induced by gentrification impacted upon the unfolding of this process in the inner Sydney suburb of Glebe from 1960 to 1986. By using an empirical analysis he reveals that a synchronisation existed between the market behaviour of small-scale property owners, working-class incumbent upgraders, and middle-class homebuyers and renters which had a significant bearing upon both the timing and the extent of gentrification activity in the case study. In addition, once a less orthodox method of measurement was employed, social replacement was found to operate alongside social displacement. The implications of these findings suggest that the process of gentrification is much more complex than has been previously inferred in the empirical literature and that this particular form of neighbourhood change can follow a number of possible trajectories, as has been more recently asserted in cross-cultural research.

A study was made on the ion exchange behavior of radiostrontium in a natural clinoptilolite and mordenite and in the synthetic zeolite A, using batch experiments over 20 days. The overall radiostrontium adsorption potential of these zeolites was measured, and the relative effect of Mg and K ions on the radiostrontium adsorption potential was assessed. A multisite model was applied to describe the change of the Sr-Ca selectivity coefficient as a function of the Sr-loading. The relevance of these results in regard to the potential use of these zeolites as countermeasure amendments in radiostrontium contaminated soils is discussed.

Zeolites of the clinoptilolite and mordenite type have been frequently proposed as countermeasure amendments to reduce radiocaesium soil-to-plant transfer in contaminated soils. The radiocaesium ion exchange behavior has been studied on a natural clinoptilolite and on a natural and a synthetic mordenite, in order to obtain quantitative data on the radiocaesium sorption competition of these zeolites relative to soils. The relative effect of K, NH 4 , and Ca—the most important competitive cations under soil conditions—was assessed, and a multisite ion exchange model has been applied to describe the change of the Cs-K selectivity coefficient as a function of the Cs loading. The relevance of the results in regard to the potential use of these zeolites as countermeasure amendments in radiocaesium-contaminated soils is discussed.

The C 2 Π and D 2 Σ + states of CaF have been investigated using three different laser-based techniques: laser excited Fourier transform-dispersed fluorescence, optical-optical double resonance, and fluorescence excitation spectroscopy. A perturbation between C 2 Π, v = 0 and D 2 Σ + , v = 0 has been observed and analyzed. Molecular Constants are reported for the C and D states. [formula]

Microscopic colitis causes chronic watery diarrhoea. Recent studies have suggested an aetiological role for various medications, including proton pump inhibitors, in the pathogenesis of microscopic colitis.To determine whether an association exists between microscopic colitis and proton pump inhibitor use in patients with documented microscopic colitis vs. age- and gender-matched controls.In this retrospective case-control study, cases of microscopic colitis from a secondary and tertiary referral medical centre diagnosed in the last 5 years were reviewed. Demographic characteristics, clinical, histological and endoscopic records, as well as exposure to PPIs and NSAIDs were assessed. Controls from the population were matched to cases by gender and by age.During the investigated period, 136 cases were identified in both hospitals. Of these, 95 cases of microscopic colitis were retrieved for detailed analysis. Exposure to proton pump inhibitors at the time of the histological diagnosis was significantly higher in patients with collagenous colitis than in controls [38% vs. 13%, P0.001; adjusted OR of 4.5 (95% CI 2.0-9.5)].This observation confirms the presumed association between microscopic colitis and PPI use, and it supports the possible aetiological role of PPI exposure in the development of microscopic colitis.

Background The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire is one of the best-characterized disease-specific instruments that captures health-related problems and symptom-patterns in patients with gastroesophageal reflux disease (GERD). This paper reports the psychometric validation of a Dutch translation of the QOLRAD questionnaire in gastroenterology outpatients with GERD. Methods Patients completed the QOLRAD questionnaire at visit 1 (baseline), visit 2 (after 2, 4 or 8 weeks of acute treatment with esomeprazole 40 mg once daily), and visit 4 (after 6 months with on-demand esomeprazole 40 mg once daily or continuous esomeprazole 20 mg once daily). Symptoms were assessed at each visit, and patient satisfaction was assessed at visits 2 and 4. Results Of the 1166 patients entered in the study, 97.3% had moderate or severe heartburn and 55.5% had moderate or severe regurgitation at baseline. At visit 2, symptoms of heartburn and regurgitation were mild or absent in 96.7% and 97.7%, respectively, and 95.3% of patients reported being satisfied with the treatment. The internal consistency and reliability of the QOLRAD questionnaire (range: 0.83-0.92) supported construct validity. Convergent validity was moderate to low. Known-groups validity was confirmed by a negative correlation between the QOLRAD score and clinician-assessed severity of GERD symptoms. Effect sizes (1.15-1.93) and standardized response means (1.17-1.86) showed good responsiveness to change. GERD symptoms had a negative impact on patients' lives. Conclusions The psychometric characteristics of the Dutch translation of the QOLRAD questionnaire were found to be satisfactory, with good reliability and responsiveness to change, although convergent validity was at best moderate.